Kontoghiorghes George J
Postgraduate Research Institute of Science, Technology, Environment and Medicine, Limassol 3021, Cyprus.
Nutrients. 2025 Oct 17;17(20):3270. doi: 10.3390/nu17203270.
Antioxidant activity is a normal physiological function that is essential for healthy living, and it is maintained by antioxidant dietary nutrients. However, increases in free radical production and oxidative toxicity in many clinical conditions can cause serious and sometimes irreversible damage. Despite many investigations, including hundreds of clinical trials suggesting that there are health benefits obtained from the use of natural antioxidants, no antioxidant drugs have yet been developed for the treatment of any disease associated with free radical pathology. Millions of people choose to use nutraceutical and natural product antioxidants as therapeutics and also for chemoprevention against cancer and other diseases. New academic efforts and strategies are required for the development of antioxidant drugs in clinical practice in the absence of interest by the pharmaceutical and nutraceutical industries. One of the most effective antioxidant therapeutic strategies is inhibition by chelators of iron involved in the catalytic formation of free radical reactions and their associated damage. Hundreds of phytochelators have been shown to inhibit oxidative damage, similar to the iron-chelating drugs deferiprone and deferoxamine. In particular, several nutraceuticals and natural products such as ascorbic acid, quercetin, curcumin, fisetin, lipoic acid, and maltol have been shown to have high antioxidant activity and iron-binding capacity, as well as other effects on iron metabolism, in pre-clinical studies and clinical trials involving different categories of patients. For example, ascorbic acid and maltol-iron complexes are sold as pharmaceutical products for the treatment of iron deficiency. The development of nutraceuticals as antioxidant drugs may involve one or more applications, such as short- or long-term treatments, single-drug or combination therapies, and also different targets, such as the prevention, treatment, or post-treatment of diseases associated with free radical pathology as well as ferroptosis. The academic efforts surrounding the developments of iron-chelating nutraceuticals or natural products into antioxidant pharmaceuticals should fulfill all of the regulatory requirements and include clinical tests of antioxidants in rare or untreatable diseases, as well as the involvement of government translational research institutions and expert groups that specialize in regulatory drug affairs, among others.
抗氧化活性是一种正常的生理功能，对健康生活至关重要，它由膳食中的抗氧化营养素维持。然而，在许多临床情况下，自由基产生增加和氧化毒性会导致严重的、有时甚至是不可逆转的损害。尽管进行了许多研究，包括数百项临床试验表明使用天然抗氧化剂对健康有益，但尚未开发出用于治疗任何与自由基病理相关疾病的抗氧化药物。数百万人选择使用营养保健品和天然产物抗氧化剂进行治疗，以及用于癌症和其他疾病的化学预防。在制药和营养保健品行业缺乏兴趣的情况下，临床实践中开发抗氧化药物需要新的学术努力和策略。最有效的抗氧化治疗策略之一是通过螯合剂抑制参与自由基反应催化形成及其相关损害的铁。数百种植螯合剂已被证明能抑制氧化损伤，类似于铁螯合药物去铁酮和去铁胺。特别是，在涉及不同类别患者的临床前研究和临床试验中，几种营养保健品和天然产物，如抗坏血酸、槲皮素、姜黄素、非瑟酮、硫辛酸和麦芽酚，已被证明具有高抗氧化活性和铁结合能力，以及对铁代谢的其他影响。例如，抗坏血酸和麦芽酚 - 铁络合物作为治疗缺铁的药品出售。将营养保健品开发为抗氧化药物可能涉及一种或多种应用，如短期或长期治疗、单一药物或联合疗法，以及不同的靶点，如预防、治疗或治疗与自由基病理以及铁死亡相关的疾病。围绕将铁螯合营养保健品或天然产物开发为抗氧化药物的学术努力应满足所有监管要求，包括在罕见或无法治疗的疾病中进行抗氧化剂的临床试验，以及政府转化研究机构和专门从事药物监管事务的专家组的参与等。
